Gender-specific contribution of the GABA_A subunit genes on 5q33 in methamphetamine use disorder

Family and twins studies have suggested that genetic factors are involved in the development of substance use disorders. Several unrelated case/control association studies have reported associations of the GABA_A subunit genes on 5q33 with the development of alcohol dependence. We hypothesized that these particular GABA_A subunit genes also contribute to the development of methamphetamine use disorder. To test our hypothesis, we recruited cases using a series of questionnaires. Among the polymorphic SNPs, significant differences between cases and controls were identified in the female sample in the rs2279020 of the GABA_Aα1 subunit gene, and the novel SNP rs4480617 in the GABA_Aγ2 subunit gene. No associations were found in the male sample. Further haplotype analysis identified several marker blocks significantly associated with methamphetamine use disorder in females; each block consists of the rs4480617. Our study provides preliminary evidence that the GABA_A subunit genes on 5q33 may preferentially contribute to methamphetamine use disorder in females.